ArticleJournal of virology2009
Essential role for either TRS1 or IRS1 in human cytomegalovirus replication.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
70 citing papers in PubMed, 83 citations in OpenAlex.
- Article
- Human cytomegalovirus modulates mTORC1 to redirect mRNA translation within quiescently infected monocytes.Journal of virology · 2024Article
- Review
- Subviral Dense Bodies of Human Cytomegalovirus Induce an Antiviral Type I Interferon Response.Cells · 2022Article
- Antagonism of Protein Kinase R by Large DNA Viruses.Pathogens (Basel, Switzerland) · 2022Review
- Minding the message: tactics controlling RNA decay, modification, and translation in virus-infected cells.Genes & development · 2022Review
- Review
- Review
- Inhibition of PKR by Viruses.Frontiers in microbiology · 2021Review
- The Current State of Oncolytic Herpes Simplex Virus for Glioblastoma Treatment.Oncolytic virotherapy · 2021Review
- Rapid adaptation to human protein kinase R by a unique genomic rearrangement in rhesus cytomegalovirus.PLoS pathogens · 2021Article
- Murine cytomegaloviruses m139 targets DDX3 to curtail interferon production and promote viral replication.PLoS pathogens · 2020Article
- Vaccinia Virus as a Master of Host Shutoff Induction: Targeting Processes of the Central Dogma and Beyond.Pathogens (Basel, Switzerland) · 2020Review
- Species-Specific Host-Virus Interactions: Implications for Viral Host Range and Virulence.Trends in microbiology · 2020Review
- Human Cytomegalovirus Primary Infection and Reactivation: Insights From Virion-Carried Molecules.Frontiers in microbiology · 2020Review
- Global virus outbreaks: Interferons as 1st responders.Seminars in immunology · 2019Review
- Human cytomegalovirus hijacks the autophagic machinery and LC3 homologs in order to optimize cytoplasmic envelopment of mature infectious particles.Scientific reports · 2019Article
- Strategies for Success. Viral Infections and Membraneless Organelles.Frontiers in cellular and infection microbiology · 2019Review
- Viral-Mediated mRNA Degradation for Pathogenesis.Biomedicines · 2018Review
- The Interplay between Human Cytomegalovirus and Pathogen Recognition Receptor Signaling.Viruses · 2018Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Viral infections often produce double-stranded RNA (dsRNA), which in turn triggers potent antiviral responses, including the global repression of protein synthesis mediated by protein kinase R (PKR) and 2'-5' oligoadenylate synthetase (OAS). As a consequence, many viruses have evolved genes, such as those encoding dsRNA-binding proteins, which counteract these pathways. Human cytomegalovirus (HCMV) encodes two related proteins, pTRS1 and pIRS1, which bind dsRNA and can prevent activation of the PKR and OAS pathways. HCMV mutants lacking either IRS1 or TRS1 replicate at least moderately well in cell culture. However, as we demonstrate in the present study, an HCMV mutant lacking both IRS1 and TRS1 (HCMV[DeltaI/DeltaT]) has a severe replication defect. Infection with HCMV[DeltaI/DeltaT] results in a profound inhibition of overall and viral protein synthesis, as well as increased phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha). The vaccinia virus E3L gene can substitute for IRS1 or TRS1, enabling HCMV replication. Despite the accumulation of dsRNA in HCMV-infected cells, the OAS pathway remains inactive, even in HCMV[DeltaI/DeltaT]-infected cells. These results suggest that PKR-mediated phosphorylation of eIF2alpha is the dominant dsRNA-activated pathway responsible for inhibition of protein synthesis and HCMV replication in the absence of both IRS1 and TRS1 and that the requirement for evasion of the PKR pathway likely explains the necessity for IRS1 or TRS1 for productive infection.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.